Lecithin-retinol acyltransferase is essential for accumulation of all-trans-retinyl esters in the eye and in the liver
Lecithin-retinol acyltransferase is essential for accumulation of all-trans-retinyl esters in the eye and in the liver
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DOI：
10.1074/jbc.m312410200
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发表时间：
2004-03-12
影响因子：
4.8
通讯作者：
Palczewski, K
中科院分区：
文献类型：
--
作者：
Batten, ML;Imanishi, Y;Palczewski, K
卵磷脂-视黄醇酰基转移酶(LRAT)是一种主要存在于视网膜色素上皮细胞和肝脏中的酶，它将全反式视黄醇转化为全反式视黄酸酯。在视网膜色素上皮中，LRAT在类视黄素循环中发挥关键作用，类视黄素循环是一个两细胞循环系统，补充视紫红质和视锥色素的11顺式视网膜生色团。我们通过靶向重组扰乱了小鼠Lrat基因的表达，并产生了纯合子Lrat基因敲除(Lrat-/-)小鼠。尽管LRAT在多种组织中表达，但Lrat-/-小鼠发育正常。6-8周龄Lrat-/-小鼠视网膜的组织学分析和电子显微镜显示，视杆外段比Lrat+/+小鼠短35%，而其他神经元层看起来正常。Lrat-/-小鼠在肝脏、肺、眼睛和血液中有微量的全反式视黄酸酯，而循环中的全反式视黄醇仅轻微减少。暗视和明视视网膜电图以及瞳孔收缩分析显示，视杆细胞和视锥细胞的视觉功能在很小的时候就严重减弱。我们的结论是，Lrat-/-小鼠可以作为早发性严重视网膜营养不良和严重视黄酯剥夺的动物模型。
Lecithin-retinol acyltransferase (LRAT), an enzyme present mainly in the retinal pigmented epithelial cells and liver, converts all-trans-retinol into all-trans-retinyl esters. In the retinal pigmented epithelium, LRAT plays a key role in the retinoid cycle, a two-cell recycling system that replenishes the 11-cis-retinal chromophore of rhodopsin and cone pigments. We disrupted mouse Lrat gene expression by targeted recombination and generated a homozygous Lrat knock-out (Lrat-/-) mouse. Despite the expression of LRAT in multiple tissues, the Lrat-/- mouse develops normally. The histological analysis and electron microscopy of the retina for 6-8-week-old Lrat-/- mice revealed that the rod outer segments are similar to35% shorter than those of Lrat+/+ mice, whereas other neuronal layers appear normal. Lrat-/- mice have trace levels of all-trans-retinyl esters in the liver, lung, eye, and blood, whereas the circulating all-trans-retinol is reduced only slightly. Scotopic and photopic electroretinograms as well as pupillary constriction analyses revealed that rod and cone visual functions are severely attenuated at an early age. We conclude that Lrat-/- mice may serve as an animal model with early onset severe retinal dystrophy and severe retinyl ester deprivation.